Selenium and the Course of Mild Graves’ OrbitopathyMarcocci C M.D., Kahaly GJ M.D., Krassas GE M.D., et al

Jessica Seppala and Danielle Taylor

The New England Journal of Medicine, 2011

Autoimmune disease

Most common cause of hyperthyroidism in the US, 1-2% of population

5:1 female to male ratio

30-50% of those with GD develop Graves’ orbitopathy (GO)

Current Treatment:◦ Antithyroid drugs◦ Radioiodine◦ Surgery

7

Graves’ Disease (GD)

Graves’ OrbitopathySigns/Symptoms

◦ Eyelid retraction◦ Eye irritation◦ Dryness◦ Excessive tearing◦ Visual blurring◦ Diplopia (double vision)◦ Retro-orbital discomfort◦ Pain on eye movement◦ Visual loss

Results in decreased quality of life due to decreased visual functioning and altered appearance

www.thyroidmanager.org

Functions of Selenium

Cofactor for glutathione peroxidase◦ Catalyzed the removal of H2O2 or lipid peroxide

Cofactor for thioredoxin reductase◦ Similar to rxn with glutathione peroxidase, involved in oxidation-reduction reaction

Selenoprotein P◦ Major selenium containing protein in the blood, thought to function as an antioxidant

Selenoprotein W◦ Thought to function as an antioxidant

Needed for iodine metabolism and regulates thyroid hormone production

3

http://lpi.oregonstate.edu/infocenter/vitamins/riboflavin/GSH.html

Purpose of the StudyDetermine if selenium or pentoxifylline

are effective treatments for Graves’ orbitopathy.◦ In vitro studies have shown increased

production of free radicals in Graves’ orbitopathy Superoxide radical production stimulates

retroocular fibroblast proliferation. ◦Pentoxifylline shown in a pilot study to be

beneficial Pentoxifylline is a phosphodiesterase inhibitor Anti-inflammatory and immunomodulatory effects

Methods

Primary End Points MeasuredEvaluated at baseline, 3, 6 and 12 months

◦ Eye examination by an ophthalmologist eyelid aperture size, soft tissue involvement,

exophthalmos, eye-muscle involvement, and visual acuity

◦ Graves’ Orbitopathy-Quality Of Life questionnaire (GO-QOL) A score of 1, 2, or 3 is assigned to each of the eight

questions in each subscale. 1 = seriously limited 2 = a little limited 3 = not at all limited 0 full limitation to 100 no limitation

An increase in the score of 6+ indicates clinical improvement

A decrease indicates worsening

Secondary End Points Measured

◦7 item - Clinical Activity Score Final score is sum of all items present

◦Gorman diplopia score Four categories

No diplopia, diplopia at extremes of gaze,diplopia when pt is tired or awakening,continuous diplopia in the primary or reading position

◦Blood samples Assessed thyroid function and autoantibodies

against thyroid peroxidase and thyrotropin receptor

◦All side effects of treatments were recorded

File:Diplopia.jpg From Wikipedia, the free encyclopedia

Results GO-QOL 6 months:◦ GO-QOL scores

increased 6+ points for 62% and 75% for visual functioning and appearance respectively in selenium group

◦ Selenium group had significantly improved QOL vs placebo group and lower rate of worsening QOL

Overall Eye Evaluation 6 months:◦ Better in selenium group

than placebo group◦ No significant difference

between pentoxifylline and placebo group

◦ Adverse side effects

Beneficial effects of selenium on QOL and eye evaluation persisted after treatment was withdrawn

ConclusionsThe beneficial effects detected at 6

months persisted for 6 months after selenium therapy was withdrawn

Selenium supplementation for 6 months improves the quality of life and overall eye function in patients with mild Graves’ orbitopathy

LimitationsLack of data on serum selenium levels

before and after sodium selenite administration

Lack of measuring patient compliance Did not assess diets of the

participants before or during the study

Smokers were not excludedDifferent ophthalmologists per center

patients.about.com

Questions What is one of the main functions

of selenium in the body?

Based on this knowledge, can you think of any other nutrients we have discussed in class that could be used in the treatment of Graves’ orbitopathy?

An antioxidant

References1. Marcocci C M.D., Kahaly GJ M.D., Krassas GE M.D., et al. Selenium

and the Course of Mild Graves’ Orbitopathy. The New England Journal of Medicine. 2011:364:1920-1931.

2. Ginsberg J. Diagnosis and management of Graves’ disease. Canadian Medical Association Journal. 2003:168:575-585.

3. Gropper SS, Smith JL, Groff JL. Advanced Nutrition and Human Metabolism. 5th ed. Belmont, CA: Wadsworth; 2009

4. Burch HB, Lahiri S, Bahn RS, Barnes S. Superoxide radical production stimulates retroocular fibroblast proliferation in Graves’ ophthalmopathy. Exp Eye Res 1997; 65:311-6.

5. Prabhakar BS, Bahn RS, Smith TJ. Current Perspective on the Pathogenesis of Graves’ Disease and Ophthamopathy. Endocrine Reviews 2003;24(6):802-835.

6. Bartalana L, Baldeschi L, Dickinson A, et al. Consensus statement of the European Group on Graves’ Orbitopathy (EUGOGO) on management of GO. Eur J Endocrinol 2008;158:273-85.

7. Duntas LH. The Evolving Role of Selenium in the Treatment of Graves’ Disease and Ophthalmopathy. Journal of Thyroid Research. 2012:2012:1-6